Agmatine, which in other life forms serves as a metabolic intermediate for polyamine biosynthesis, appears to have properties in mammals consistent with its actions as a neurotransmitter/neuromodulator. Thus, agmatine is synthesized unequally in brain by arginine decarboxylase (ADC); is stored in neurons and axon terminals with a heterogeneous distribution; is released from synaptosomes by depolarization; is enzymatically converted by agmatinase to putrescine; interacts not only with alpha2-adrenergic and I-receptors in the CNS, but also may selectively block NMDA receptor channels; and, when administered centrally, has several potent biological actions. Clarification of its role in normal brain function, however, has not yet been fully established, in part because of the absence of agents that selectively affect its biosynthesis or degradation.